In mammals, including man, the male generally ages faster and dies earlier than the female. This may be due to the faster accumulation of X-linked deleterious mutations by male somatic cells. Conversely, the male's androgenic steroid hormone might be a potent aging agent. The cause of sexual difference is often hard to untangle. For example, the reason why the female is more immune competent than the male is not very clear. We propose to untangle these problems by the combined use of the X-linked testicular feminization (Tfm) gene and the autosomal dominant sex reversal (Sxr) gene of the mouse. The Tfm mutation renders all the somatic cells completely nonresponsive to androgen. Thus, in the body of Tfm/Y male/female, XY cells escape from the effect of androgen. Conversely, in the body of sex reversed XX, Sxr/ plus male, XX-cells come under the influence of androgen. Of course, some somatic cells are more important than others. For example, many somatic cells would be affected by the malfunction of hypothalamus. The Tfm mutation being X- linked, Tfm/ plus, Sxr/ plus male are mosaics being made of androgen- responsive plus -cells and nonresponsive Tfm cells. With a certain frequency, each somatic cell type of the heterozygous body would become effectively Tfm-monoclonal. This would enable us to analyze the contribution of individual somatic cell types to the sex-related ageing process.